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- | Journal: Immune alterations in subacute sclerosing panencephalitis reflect an incompetent response to eliminate the measles virus. (Pubmed Central) - May 11, 2021
The immune response did not reveal an inflammatory activity to eliminate the virus in SSPE patients. Even IL-10 production was diminished implicating that the response is self-limited in controlling the disease.
- | Journal: Decrease of laminin-511 in the basement membrane due to photoaging reduces epidermal stem/progenitor cells. (Pubmed Central) - May 4, 2021
Combined treatment with matrix metalloproteinase and heparanase inhibitors protected the integrity of laminin-511 and inhibited the reduction of MCSP-positive cells and K15-positive cells. These results suggest that photoaging may reduce the levels of MCSP-positive and K15-positive epidermal stem/progenitor cells in the epidermis via loss of laminin-511 at the dermal-epidermal junction.
- [VIRTUAL] Sonication Linker Mediated-PCR (SLiM-PCR), an Efficient Method for Quantitative Retrieval of Vector Integration Sites () - Apr 30, 2021 - Abstract #ASGCT2021ASGCT_875;
Overall, we retrieved >200,000 IS from in vitro and in vivo samples and found that the progeny of infused CAR T cells was able to engraft, expand, and persist over time. At later time points, the clonal repertoire was markedly reduced, in agreement with the contraction phase after tumor clearance.In summary, our results show that SLiM-PCR is a powerful method for IS retrieval and accurate clonal abundance estimation and that can be applied to a broad spectrum of gene therapy platforms.
- [VIRTUAL] Toward Persistent Control of HIV Infection by Expressing a Highly Potent HIV Decoy Receptor after In Vivo HSC Transduction () - Apr 30, 2021 - Abstract #ASGCT2021ASGCT_752;
Using an GFP reporter, we have observed that in vivo transduction in mice with HDAd5/35++ vectors led to 7% transgene expression in total bone marrow LLPCs. Since no selection is needed, this application could generate high level eCD4-Ig production shortly after vector injection.
- Actemra IV (tocilizumab) / Roche, JW Pharma
[VIRTUAL] In Vivo HSC Gene Therapy with High-Level, Erythroid-Specific Expression of a Secreted SARS-CoV-2 Decoy Receptor () - Apr 30, 2021 - Abstract #ASGCT2021ASGCT_177;
The HSC transduction efficacy and serum sACE2-Ig levels after in vivo selection will be reported. Ultimately, we plan to test whether continuous sACE2-Ig expression could provide protection against challenges with CoV-2 variants in the mouse and NHP models.
- [VIRTUAL] Preclinical Toxicology Assessment of an Oncolytic Measles Virus Armed with H. pylori Immunostimulatory Bacterial Antigen in Preparation for a Phase I Trial in Breast Cancer Patients () - Apr 30, 2021 - Abstract #ASGCT2021ASGCT_8;
This outcome supports the safety of the MV-sNAP platform for oncolytic virotherapy of MBC. Enrollment in a Phase I clinical trial of MV-sNAP in patients with MBC (NCT 04521764) started in November 2020.
- || Review, Journal: The Complement System in the Pathophysiology of Pregnancy and in Systemic Autoimmune Rheumatic Diseases During Pregnancy. (Pubmed Central) - Apr 29, 2021
In other diseases, such as preeclampsia, the mechanism of complement activation responsible for complement deposits in placenta is unclear. Conflicting results have been reported on the relevance of complement assays as diagnostic and prognostic tools to assess complement involvement in pregnant patients with these disorders.
- | Journal: The expression of membrane-bound complement regulatory proteins CD46, CD55 and CD59 in oral lichen planus. (Pubmed Central) - Apr 28, 2021
These results suggest that the reduced expression of mCRPs keeps the complement system in a continuously active state, which may be the reason of the persistent local immune inflammatory state in OLP. This study aimed to provide new insights for the etiology and therapy of OLP.
- | Journal: The landscape of alternative splicing in HIV-1 infected CD4 T-cells. (Pubmed Central) - Apr 23, 2021
This study aimed to provide new insights for the etiology and therapy of OLP. Our findings may provide new insight into systemic host AS regulation under HIV-1 infection and may provide useful initial candidates for the discovery of new markers for specifically targeting infected T-cells.
- | Journal: Complement Regulation in Human Tenocytes under the Influence of Anaphylatoxin C5a. (Pubmed Central) - Apr 22, 2021
Hence, exposure of tenocytes to C5a obviously evokes a time and concentration-dependent response in their expression of complement and pro-inflammatory factors. C5a, released in damaged tendons, might directly contribute to tenocyte activation and thereby be involved in tendon healing and tendinopathy.
- | Journal: Sperm Cholesterol Content Modifies Sperm Function and TRPV1-Mediated Sperm Migration. (Pubmed Central) - Apr 22, 2021
Accordingly, CD:Epi-Chol was significantly less efficient than CD:Chol, in reducing sperm migration under CPS gradient. Chol inhibits TRPV1-mediated sperm function by directly interacting with a consensus sequence of the receptor.
- ||| Vaxzevria (ChAdOx1-S recombinant) / Oxford Biomedica, Emergent Biosolutions, Jenner Institute, Vaccitech, AstraZeneca, University of Oxford
J&J argues that their vaccine Ad26 “is from Ad species D and can engage CD46 as its cellular receptor, whereas ChAdOx1 nCoV-19 (AZ) is from Ad species E and uses the Coxsackie and adenovirus receptor (CAR) and possibly other molecules as its cellular receptors” (Twitter) - Apr 16, 2021
- | Sarclisa (isatuximab-irfc) / Sanofi
Journal, PD(L)-1 Biomarker, IO biomarker: Isatuximab Acts Through Fc-Dependent, Independent, and Direct Pathways to Kill Multiple Myeloma Cells. (Pubmed Central) - Apr 13, 2021
Finally, isatuximab-induced CDC was observed in cell lines with high CD38 receptor density (>250,000 molecules/cell) and limited expression of inhibitory complement regulatory proteins (CD46, CD55, and CD59; <50,000 molecules/cell). Taken together, our findings highlight mechanistic insights for isatuximab and provide support for a range of combination therapy approaches that could be tested for isatuximab in the future.
- || Soliris (eculizumab) / Alexion Pharma
Clinical, Journal: Cocaine-associated atypical haemolytic uraemic syndrome in a genetically susceptible individual. (Pubmed Central) - Mar 30, 2021
The patient was found to have a rare genetic variant in the CFI gene which may have been unmasked by first-time exposure to cocaine. The patient stabilised and improved with early administration of eculizumab, supporting the notion of an underlying immunological pathogenesis and the importance of early intervention.
- | Journal: CD46 splice variant enhances translation of specific mRNAs linked to an aggressive tumor cell phenotype in bladder cancer. (Pubmed Central) - Mar 27, 2021
Strikingly, the splicing factor SRSF1 is highly correlated with CD46 exon 13 exclusion in clinical BCa samples. Taken together, our findings contribute to understanding the role of CD46 in BCa development.
- | Blenrep (belantamab mafodotin) / GSK
Journal: Bispecifics, trispecifics, and other novel immune treatments in myeloma. (Pubmed Central) - Mar 26, 2021
Belantamab mafodotin, a B-cell maturation antigen (BCMA)-targeted ADC, has shown response rates >30% in a phase 2 trial of highly refractory patients and is being investigated in a variety of settings and combinations...This is an area of active preclinical research at this time. Lastly, designed ankyrin repeat proteins, which are small antibody-mimetic proteins with high target-binding affinity, have the potential to block multiple pathways at once and provide stimulatory signals to the immune system.
- | Qarziba (dinutuximab beta) / BeiGene, Jazz
Journal, IO biomarker: GD2 targeting by dinutuximab beta is a promising immunotherapeutic approach against malignant glioma. (Pubmed Central) - Mar 16, 2021
Our present data show anti-tumor effects mediated by dinutuximab beta against GBM cells providing a rationale for a GD2-directed immunotherapy against GBM. Due to high CRP expression, a combining of GD2-targeting with CRP blockade might be a further treatment option for GBM.
- || Review, Journal, Oncolytic virus: Adenovirus Receptor Expression in Cancer and Its Multifaceted Role in Oncolytic Adenovirus Therapy. (Pubmed Central) - Mar 16, 2021
Additionally, the utility of the adenovirus receptors in oncolytic virotherapy is examined, including their role in viral spread, which might even surpass their function as primary entry receptors. Finally, future directions are offered regarding the selection of adenovirus types to be used in oncolytic adenovirus therapy in the fight against cancer.
- | Journal: Does expression of a human complement-regulatory protein on xenograft cells protect them from systemic complement activation? Experimental research. (Pubmed Central) - Mar 16, 2021
Finally, future directions are offered regarding the selection of adenovirus types to be used in oncolytic adenovirus therapy in the fight against cancer. The expression of hCD46 protected pAECs from systemic complement activation.
- || Clinical, Journal: mRNA expression disturbance of complement system related genes in acute arterial thrombotic and paroxysmal atrial fibrillation patients. (Pubmed Central) - Feb 25, 2021
Taken SAP patients as controls, the complement system is in a high-intensive disturbance with simultaneous activation and inhibition in AMI patients, indicating that the cascade response of complement system is disturbed, and then the membrane attack complex (MAC) cannot form finally. The mRNA expression of related genes in the complement system is under a status of downregulation in PAF patients, indicating that the functions of cascade response in the complement system decreased significantly in PAF patients, leading to significantly decreased MAC functions.
- | Preclinical, Journal: A CRISPR/Cas9 Generated Bovine CD46-knockout Cell Line-A Tool to Elucidate the Adaptability of Bovine Viral Diarrhea Viruses (BVDV). (Pubmed Central) - Feb 24, 2021
In the fourth isolate, the exchange of a cysteine at position 441 in the E resulted in a loss of E dimerization that is likely to influence viral cell-to-cell spread. In general, the CD46-knockout cell line is a useful tool to analyze the role of CD46 for pestivirus replication and the virus-receptor interaction.
- | Journal: House Dust Mite Exposure Causes Increased Susceptibility of Nasal Epithelial Cells to Adenovirus Infection. (Pubmed Central) - Feb 24, 2021
Furthermore, electron microscopic and histologic analyses of 3D cell cultures revealed an impairment of the respiratory cilia after HDM exposition. This ex vivo pilot study shows the impact of AdV infection and HDM exposition in a primary cell culture model for asthma.
- | Journal, Oncolytic Virus, IO biomarker: Efficient antitumor effects of a novel oncolytic adenovirus fully composed of species B adenovirus serotype 35. (Pubmed Central) - Feb 23, 2021
OAd35 significantly suppressed growth of the subcutaneous CAR-positive and CAR-negative tumors following intratumoral administration. These results indicated that OAd35 is a promising alternative oncolytic virus for OAd5.
- | Journal: Vitamin E can promote spermatogenesis by regulating the expression of proteins associated with the plasma membranes and protamine biosynthesis. (Pubmed Central) - Feb 20, 2021
We found that many of the differentially expressed proteins, such as CD46 (membrane cofactor protein), FLNA (Filamin A), DYSF (Dysferlin), IFT20 (Intraflagellar transport 20), SPCS1 (Signal peptidase complex subunit 1) and SPCS3 (Signal peptidase complex subunit 3) were related to the acrosomal and plasma membranes. A parallel reaction monitoring (PRM) analysis verified that Vitamin E improved spermatogenesis by regulating the expression of FLNA, SPCS3, YBX3 and RARS, proteins that are associated with the plasma membranes and protamine biosynthesis of the spermatozoa.
- || Review, Journal: Human adenovirus binding to host cell receptors: a structural view. (Pubmed Central) - Feb 11, 2021
The diversity of HAdV receptors contributes to the broad tropism of these viruses, and structural studies are thus an important source of information on HAdV-host cell interactions. The imbalance in structural data between the more and less extensively studied receptors remains to be addressed by future research.
- || PK/PD data, Journal: Transport of Extracellular Vesicles across the Blood-Brain Barrier: Brain Pharmacokinetics and Effects of Inflammation. (Pubmed Central) - Feb 10, 2021
A brain-to-blood efflux mechanism variably affected CNS retention and explains how CNS-derived exosomes enter blood. In summary, all exosomes tested here readily crossed the BBB, but at varying rates and by a variety of vesicular-mediated mechanisms involving specific transporters, adsorptive transcytosis, and a brain-to-blood efflux system.
- || Review, Journal: Treating Prostate Cancer by Antibody-Drug Conjugates. (Pubmed Central) - Feb 10, 2021
Therefore, we focus on recently published and ongoing trials designed to investigate the clinical activity of ADCs against prostate malignancy, characterizing these agents. Lastly, we briefly discuss some ADCs-related issues with corresponding strategies to overwhelm them, along with future perspectives for these promising novel compounds.
- | Journal: Real Time Analysis of Bovine Viral Diarrhea Virus (BVDV) Infection and Its Dependence on Bovine CD46. (Pubmed Central) - Feb 9, 2021
These results indicate that the presence of bovine CD46 is only affecting the speed of directed transport, but otherwise not influencing BVDV cell surface motility. Instead, bovine CD46 seems to be an important factor during uptake, suggesting the presence of additional cellular proteins interacting with the virus which are able to support its transport on the virus surface.
- | Journal: Xenograft-derived mRNA/miR and protein interaction networks of systemic dissemination in human prostate cancer. (Pubmed Central) - Feb 9, 2021
The clinical and functional relevance of the dissemination-related interaction networks shown here could be successfully validated by proof-of-principle experiments. Therefore, we suggest a direct pro-metastatic, clinically relevant role for the multiple novel candidates included in this study; these should be further exploited by future studies.
- [VIRTUAL] Functional Characterization of the Orphan Nuclear Receptor TLX in Triple Negative Breast Cancer (On-Demand) - Feb 2, 2021 - Abstract #ENDO2021ENDO_2163;
For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021.
- | Journal: The tetraspanin protein CD9 modulates infection with human herpesvirus 6A and 6B in a CD46-dependent manner. (Pubmed Central) - Jan 29, 2021
Moreover, elimination of CD9 and subsequent reconstitution experiments demonstrated that CD9 promoted infection with HHV-6A and HHV-6B mediated by CD46, but inhibited infection with HHV-6B that occurred independent of CD46. Together, this demonstrated a CD46-dependent role of CD9 during infection with HHV-6A and HHV-6B and emphasized that HHV-6B may employ different entry mechanisms in various cells.
- || Our genetic center tests for 13 genes: CFH, CFI, CD46, C3, the 5 CFHR related genes, ADAMTS13, THBD, DGKE and the CFHR3-1 deletion. More details on https://t.co/D5Qm65HWed. (Twitter) - Jan 21, 2021
- || Clinical, Observational data, Journal: The complement system in primary Sjögren's syndrome: the expression of certain cascade and regulatory proteins in labial salivary glands - observational study. (Pubmed Central) - Jan 20, 2021
Low MCP expression in pSS in comparison with non-specific sialadenitis and normal salivary glands, may suggest altered modulation of cell-mediated immunity in pSS. The differences in the location and intensity of protectin (CD59) expression indicates a possibility of reducing the proinflammatory effect of protectin in pSS.
- | Journal: Ayu (Plecoglossus altivelis) CD46 isoforms protect the cells from autologous complement attack. (Pubmed Central) - Jan 16, 2021
The isoforms were also identified for their protection of autologous PBMC from complement activation. These results provided the first evidence that PaCD46 isoforms may be complement regulatory proteins to prevent complement-induced damage to self-tissue.
- | Journal: Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46. (Pubmed Central) - Jan 12, 2021
Finally, soluble CD46 inhibited infection by 16 out of 17 investigated HAdV-D types, suggesting that CD46 is an important receptor for a large group of adenoviruses. In conclusion, this study identifies a noncanonical entry mechanism used by human adenoviruses, which adds to the knowledge of adenovirus biology and can also be useful for development of adenovirus-based vaccine vectors.
- | Journal, Nanostring, Gene Expression Profile, PD(L)-1 Biomarker, IO biomarker: Immune gene expression profiles in high-grade urothelial carcinoma of the bladder: a NanoString study. (Pubmed Central) - Jan 5, 2021
In conclusion, this study identifies a noncanonical entry mechanism used by human adenoviruses, which adds to the knowledge of adenovirus biology and can also be useful for development of adenovirus-based vaccine vectors. We report key genes and pathways in the immune transcriptome and their association with PD-L1 status, which may be involved in immune evasion of HGUC and warrants further investigation.
- Soliris (eculizumab) / Alexion Pharma
[VIRTUAL] Clinical characteristics and outcomes in patients treated with eculizumab for suspected atypical haemolytic uraemic syndrome (aHUS) – a single tertiary centre experience () - Jan 5, 2021 - Abstract #BSHI2020BSH-I_240;
This study demonstrates the diversity of clinical characteristics in patients suspected to have aHUS, emphasising the need for timely, pro‐active, management ensuring better outcomes. As with other rare diseases, there is an important argument for patients with aHUS to be referred to regional specialist centres to facilitate comprehensive care for this complex patient group.
- | Journal: Non-transmissible MV Vector with Segmented RNA Genome Establishes Different Types of iPSCs from Hematopoietic Cells. (Pubmed Central) - Dec 23, 2020
Human hematopoietic stem/progenitor cells were directly and efficiently reprogrammed to naive-like cells that could proliferate and differentiate into primed iPSCs by the same method used to establish primed iPSCs from other cell types. The novel MV vector has several advantages for establishing iPSCs and potential future applications in gene therapy.
- || Clinical, Journal: Pretransplant Genetic Susceptibility: Clinical Relevance in Transplant-Associated Thrombotic Microangiopathy. (Pubmed Central) - Dec 23, 2020
Notably, variants in exonic/splicing/UTR regions were associated with poor response and survival. Therefore, pretransplant genomic screening may be useful to intensify monitoring and early intervention in patients at high risk for TA-TMA.
- MGTA-145 / Magenta Therap, Mozobil (plerixafor) / Sanofi
[VIRTUAL] Mgta-145 and Plerixafor-Mediated HSC Mobilization Along with HDAd5/35++ Vector into Mice Allows for Efficient In Vivo HSC Transduction and Stable Gene Marking in Peripheral Blood Cells () - Dec 20, 2020 - Abstract #TCTASTCTCIBMTR2021TCT_ASTCT_CIBMTR_210;
- | Journal: gp96 is critical for both HHV-6A and HHV-6B infection. (Pubmed Central) - Dec 20, 2020
We identified a novel cellular factor, gp96, that is critical for both HHV-6A and -6B entry into host cells. As gp96 can function as an adjuvant in vaccine development for both infectious agents and cancers, it can be a potential therapeutic target for infection by these two viruses.
- | Journal: Impaired tumor necrosis factor-α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze. (Pubmed Central) - Dec 18, 2020
We demonstrated lower TNF-α production by in vitro stimulated CD4+ T cells during severe RSV bronchiolitis in children that subsequently developed recurrent wheezing, compared with children with no subsequent wheeze. These findings support the role of CD4+ T cell immunity in the development of subsequent wheezing in these children.
- | Journal: Common variants of fetal and maternal complement genes in preeclampsia: pregnancy specific complotype. (Pubmed Central) - Dec 17, 2020
Placental complement deposition and maternal alternative pathway 50 (AP50) values were higher in PE pregnancies. Irrespective of disease status, two CD46 variants were associated with reduced placental CD46 expression and one CFH variant was associated with increased maternal AP50 values.
- | Journal: The Combination of gQ1 and gQ2 in Human Herpesvirus 6A and 6B Regulates the Viral Tetramer Function for Their Receptor Recognition. (Pubmed Central) - Dec 12, 2020
When gQ1 or gQ2 was switched in HHV-6A and -6B, no cell fusion was observed via CD134. HHV-6B gQ2 could not complement the function of HHV-6A's gQ2 in HHV-6A propagation, suggesting that the combination of gQ1 and gQ2 is critical to regulate the specificity of the tetramer's function for virus entry.
- | Journal: A genetic variant in the promoter of CD46 is associated with the risk and prognosis of hepatocellular carcinoma. (Pubmed Central) - Dec 2, 2020
Furthermore, Cox regression analysis revealed that the rs2796267 AG/GG genotype was significantly associated with worse prognosis of resected patients with HCC (hazard ratio = 2.27; 95% CI, 1.27-4.05; P = .006). These results suggest that the CD46 rs2796267 polymorphism may contribute to susceptibility and prognosis of HCC by altering promoter activity.
- | Journal: Human desmoglein-2 and human CD46 mediate HAdV55 infection but human desmoglein-2 plays the major roles. (Pubmed Central) - Dec 1, 2020
hDSG2 transgenic mice enabled more efficient HAdV55 infection than hCD46 transgenic mice. Our study adds to our understanding of HAdV55 infection and provides an animal model for evaluating HAdV55 vaccines and therapeutics.
- | Journal: Molecular Studies and an ex vivo Complement Assay on Endothelium Highlight the Genetic Complexity of Atypical Hemolytic Uremic Syndrome: The Case of a Pedigree With a Null CD46 Variant. (Pubmed Central) - Nov 25, 2020
These results highlight the complexity of the genetics of aHUS and indicate that CD46 deficiency may not be enough to induce aHUS. We hypothesize that the proband inherited from his mother a genetic abnormality in a complement circulating factor that has not been identified yet, which synergized with the CD46 RV in predisposing him to the aHUS phenotype.
- | Journal, IO Biomarker: Salidroside Restores an Anti-inflammatory Endothelial Phenotype by Selectively Inhibiting Endothelial Complement After Oxidative Stress. (Pubmed Central) - Nov 19, 2020
These results suggest endothelium is an important locus of inhibition of complement by salidroside, restoring an anti-inflammatory endothelial phenotype after oxidative stress, partly by inhibiting classical complement activation and partly by increasing CD46 and CD59, in association with anti-apoptotic effects. These endothelial effects may contribute to the protection afforded by salidroside in cerebral ischemia-reperfusion injury.
- || Alofisel (darvadstrocel) / Takeda
Clinical, Journal, IO Biomarker: Dissecting Allo-Sensitization After Local Administration of Human Allogeneic Adipose Mesenchymal Stem Cells in Perianal Fistulas of Crohn's Disease Patients. (Pubmed Central) - Nov 12, 2020
The present study aims to assess allo-immune responses in a cohort of Crohn's disease patients administered with allogeneic ASC (darvadstrocel formerly Cx601) for the treatment of complex perianal fistulas...It is still unknown whether DSA generation could potentially be the consequence of donor-to-patient interaction and, therefore, subsequently link to efficacy or biological activity. Lastly, we propose that CDC modulators such as CD46 could be used to ultimately link CDC specificity with allogeneic cell therapy efficacy.
- || Review, Journal: CD46 and Oncologic Interactions: Friendly Fire against Cancer. (Pubmed Central) - Nov 6, 2020
As a result, there are multiple early-phase clinical trials targeting CD46 to treat a variety of cancers. Here, we review CD46 relative to these oncologic connections.